Giving fat rats a gene therapy jab helps them to lose weight by turning their fat-storing cells into fat-burning cells, according to a new study.
A team of US and Swiss scientists used a virus to deliver the gene for the fat-busting hormone leptin to the fat-storing cells of rats predisposed to diabetes.
Within two weeks the rats shed over a quarter of their weight and their appetite decreased by a third. The leptin appeared to convert cells which normally stockpile fat into lean, fatless cells.
“This is the first careful examination of the fat cells after leptin therapy,” says Roger Unger of the University of Texas Southwestern Medical Center in Dallas, US, and one of the team.
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“The structure of the cells changed from the normal appearance of a fat cell to a very novel cell that’s really never been seen before,” he says. “The ability to convert fat cells into fat-burning cells may suggest novel therapeutic strategies for obesity.”
“It’s a fascinating paper,” says Steve Bloom, a leading obesity researcher at Imperial College London, UK. But he cautions: “It’s unexpected and very interesting – though against conventional wisdom.”
He told New Scientist that previous trials using “vast amounts” of leptin in obese humans over many months had no effect on weight loss. But he adds that, if confirmed, the new results may hold some promise.
Plummeting weight
Unger and colleagues gave the rats an intravenous injection of adenovirus containing the gene for leptin. The protein was then produced by the rats’ livers, rising to 50 times its normal level in rats after two to four days.
The animals receiving leptin showed a rapid loss in weight compared with those placed on a restricted diet. “After 14 days, rats receiving leptin injections plummeted on average from 280 to 207 grams,” says Unger.
These rats appeared to suffer no side-effects and had a 30 per cent reduction in food intake. However, the rats put on a diet were constantly seeking food and reduced their physical activity.
When the team examined the rats’ fat-storing cells, called adipose cells, they discovered “profound morphological and molecular changes” in response to leptin therapy. The cells had become crammed with tiny cellular organelles called mitochondria, which act as power packs in cells – burning oxygen and providing energy.
“As a principle, increasing the energy expenditure in fat cells is clearly a very useful way forward,” says Bloom. “But at the moment leptin is a very, very long way from being a therapy for humans.”
Journal reference: Proceedings of the National Academy of Sciences (vol 101, p 2058)
